Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial
Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 study showed that ozanimod had better efficacy than placebo on MRI measures, with a favourable safety profile, in participants with relapsing multiple scler...
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| Veröffentlicht in: | Lancet neurology 2019-11, Vol.18 (11), p.1009-1020 |
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| creator | Comi, Giancarlo Kappos, Ludwig Selmaj, Krzysztof W Bar-Or, Amit Arnold, Douglas L Steinman, Lawrence Hartung, Hans-Peter Montalban, Xavier Kubala Havrdová, Eva Cree, Bruce A C Sheffield, James K Minton, Neil Raghupathi, Kartik Ding, Ning Cohen, Jeffrey A |
| description | Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 study showed that ozanimod had better efficacy than placebo on MRI measures, with a favourable safety profile, in participants with relapsing multiple sclerosis. The SUNBEAM study aimed to assess the safety and efficacy of ozanimod versus intramuscular interferon beta-1a in participants with relapsing multiple sclerosis.
SUNBEAM was a randomised, double-blind, double-dummy, active-controlled phase 3 trial done at 152 academic medical centres and clinical practices in 20 countries. We enrolled participants aged 18–55 years with relapsing multiple sclerosis, baseline expanded disability status scale (EDSS) score of 0·0–5·0, and either at least one relapse within the 12 months before screening or at least one relapse within 24 months plus at least one gadolinium-enhancing lesion within 12 months before screening. Participants were randomly assigned 1:1:1 by a blocked algorithm stratified by country and baseline EDSS score to at least 12 months treatment of either once-daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment assignment. The primary endpoint was annualised relapse rate (ARR) during the treatment period and was assessed in the intention-to-treat population. Safety was assessed in all participants according to the highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, number NCT02294058 and EudraCT, number 2014–002320–27.
Between Dec 18, 2014, and Nov 12, 2015, 1346 participants were enrolled and randomly assigned to ozanimod 1·0 mg (n=447), ozanimod 0·5 mg (n=451), or interferon beta-1a (n=448). 91 (6·8%) participants discontinued the study drug (29 in the ozanimod 1·0 mg group; 26 in the ozanimod 0·5 mg group; and 36 in the interferon beta-1a group). Adjusted ARRs were 0·35 (0·28–0·44) for interferon beta-1a, 0·18 (95% CI 0·14–0·24) for ozanimod 1·0 mg (rate ratio [RR] of 0·52 [0·41–0·66] vs interferon beta-1a; p |
| doi_str_mv | 10.1016/S1474-4422(19)30239-X |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2286945287</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S147444221930239X</els_id><sourcerecordid>2286945287</sourcerecordid><originalsourceid>FETCH-LOGICAL-c445t-5ab3aff0cd5b6a8dafad8d44b95db996f27be0985f45b2eae000c6045bf4cee3</originalsourceid><addsrcrecordid>eNqFkc9u1DAQxiMEoqXwCCBLXLbSBmzHzia9oFKVP1KBwxapN2tij6mrxF5sp9LyMrwqbnfpgQun8Yx_M99ovqp6yegbRln7ds3EStRCcL5g_XFDedPXV4-qw325lY8f3pwfVM9SuqGUM9Gxp9VBw0TPW8kOq99rsJi3BLwhaK3ToLckWBJ-gXdTMOQWY5oTcT5jtBiDJwNmqBmUEok4wiY5_4NM85jdZkSS9Fio5BJZrL9_fX9--uX4hMDuX6PPEZckFrUwuYRmSSZXdOaJMF5PwefrJdlcQ0LSkBwdjM-rJxbGhC_28ai6_HB-efapvvj28fPZ6UWthZC5ljA0YC3VRg4tdAYsmM4IMfTSDH3fWr4akPadtEIOHAEppbqlJbFCIzZH1WI3dhPDzxlTVmU9jeMIHsOcFOdd2wvJu1VBX_-D3oQ5-rKc4g1tGJUdl4WSO0qXY6SIVm2imyBuFaPqzkB1b6C6c0exXt0bqK5K36v99HmY0Dx0_XWsAO92AJZr3DqMKmmHXqNxEXVWJrj_SPwB-bKshw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2303105825</pqid></control><display><type>article</type><title>Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial</title><source>Elsevier ScienceDirect Journals</source><creator>Comi, Giancarlo ; Kappos, Ludwig ; Selmaj, Krzysztof W ; Bar-Or, Amit ; Arnold, Douglas L ; Steinman, Lawrence ; Hartung, Hans-Peter ; Montalban, Xavier ; Kubala Havrdová, Eva ; Cree, Bruce A C ; Sheffield, James K ; Minton, Neil ; Raghupathi, Kartik ; Ding, Ning ; Cohen, Jeffrey A</creator><creatorcontrib>Comi, Giancarlo ; Kappos, Ludwig ; Selmaj, Krzysztof W ; Bar-Or, Amit ; Arnold, Douglas L ; Steinman, Lawrence ; Hartung, Hans-Peter ; Montalban, Xavier ; Kubala Havrdová, Eva ; Cree, Bruce A C ; Sheffield, James K ; Minton, Neil ; Raghupathi, Kartik ; Ding, Ning ; Cohen, Jeffrey A ; SUNBEAM Study Investigators</creatorcontrib><description>Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 study showed that ozanimod had better efficacy than placebo on MRI measures, with a favourable safety profile, in participants with relapsing multiple sclerosis. The SUNBEAM study aimed to assess the safety and efficacy of ozanimod versus intramuscular interferon beta-1a in participants with relapsing multiple sclerosis.
SUNBEAM was a randomised, double-blind, double-dummy, active-controlled phase 3 trial done at 152 academic medical centres and clinical practices in 20 countries. We enrolled participants aged 18–55 years with relapsing multiple sclerosis, baseline expanded disability status scale (EDSS) score of 0·0–5·0, and either at least one relapse within the 12 months before screening or at least one relapse within 24 months plus at least one gadolinium-enhancing lesion within 12 months before screening. Participants were randomly assigned 1:1:1 by a blocked algorithm stratified by country and baseline EDSS score to at least 12 months treatment of either once-daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment assignment. The primary endpoint was annualised relapse rate (ARR) during the treatment period and was assessed in the intention-to-treat population. Safety was assessed in all participants according to the highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, number NCT02294058 and EudraCT, number 2014–002320–27.
Between Dec 18, 2014, and Nov 12, 2015, 1346 participants were enrolled and randomly assigned to ozanimod 1·0 mg (n=447), ozanimod 0·5 mg (n=451), or interferon beta-1a (n=448). 91 (6·8%) participants discontinued the study drug (29 in the ozanimod 1·0 mg group; 26 in the ozanimod 0·5 mg group; and 36 in the interferon beta-1a group). Adjusted ARRs were 0·35 (0·28–0·44) for interferon beta-1a, 0·18 (95% CI 0·14–0·24) for ozanimod 1·0 mg (rate ratio [RR] of 0·52 [0·41–0·66] vs interferon beta-1a; p<0·0001), and 0·24 (0·19–0·31) for ozanimod 0·5 mg (RR 0·69 [0·55–0·86] vs interferon beta-1a; p=0·0013). Few ozanimod-treated participants discontinued treatment because of adverse events (13 [2·9%] who received ozanimod 1·0 mg; seven [1·5%] who received ozanimod 0·5 mg; and 16 [3·6%] who received interferon beta-1a). No first-dose, clinically significant bradycardia or second-degree or third-degree atrioventricular block was reported. The incidence of serious adverse events was low and similar across treatment groups (13 [2·9%] participants who received ozanimod 1·0 mg; 16 [3·5%] who received ozanimod 0·5 mg; and 11 [2·5%] who received interferon beta-1a). No serious opportunistic infections occurred in ozanimod-treated participants.
In participants with relapsing multiple sclerosis treated for at least 12 months, ozanimod was well tolerated and demonstrated a significantly lower relapse rate than interferon beta-1a. These findings provide support for ozanimod as an oral therapy for individuals with relapsing multiple sclerosis.
Celgene International II.</description><identifier>ISSN: 1474-4422</identifier><identifier>EISSN: 1474-4465</identifier><identifier>DOI: 10.1016/S1474-4422(19)30239-X</identifier><identifier>PMID: 31492651</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Bradycardia ; Brain research ; Chicken pox ; Clinical trials ; Drug dosages ; Edema ; Gadolinium ; Heart ; Heart rate ; Infections ; Interferon ; Ligands ; Lymphocytes ; Magnetic resonance imaging ; Multiple sclerosis ; Safety ; Sphingosine 1-phosphate ; Studies</subject><ispartof>Lancet neurology, 2019-11, Vol.18 (11), p.1009-1020</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>2019. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-5ab3aff0cd5b6a8dafad8d44b95db996f27be0985f45b2eae000c6045bf4cee3</citedby><cites>FETCH-LOGICAL-c445t-5ab3aff0cd5b6a8dafad8d44b95db996f27be0985f45b2eae000c6045bf4cee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S147444221930239X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31492651$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Comi, Giancarlo</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Selmaj, Krzysztof W</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Arnold, Douglas L</creatorcontrib><creatorcontrib>Steinman, Lawrence</creatorcontrib><creatorcontrib>Hartung, Hans-Peter</creatorcontrib><creatorcontrib>Montalban, Xavier</creatorcontrib><creatorcontrib>Kubala Havrdová, Eva</creatorcontrib><creatorcontrib>Cree, Bruce A C</creatorcontrib><creatorcontrib>Sheffield, James K</creatorcontrib><creatorcontrib>Minton, Neil</creatorcontrib><creatorcontrib>Raghupathi, Kartik</creatorcontrib><creatorcontrib>Ding, Ning</creatorcontrib><creatorcontrib>Cohen, Jeffrey A</creatorcontrib><creatorcontrib>SUNBEAM Study Investigators</creatorcontrib><title>Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial</title><title>Lancet neurology</title><addtitle>Lancet Neurol</addtitle><description>Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 study showed that ozanimod had better efficacy than placebo on MRI measures, with a favourable safety profile, in participants with relapsing multiple sclerosis. The SUNBEAM study aimed to assess the safety and efficacy of ozanimod versus intramuscular interferon beta-1a in participants with relapsing multiple sclerosis.
SUNBEAM was a randomised, double-blind, double-dummy, active-controlled phase 3 trial done at 152 academic medical centres and clinical practices in 20 countries. We enrolled participants aged 18–55 years with relapsing multiple sclerosis, baseline expanded disability status scale (EDSS) score of 0·0–5·0, and either at least one relapse within the 12 months before screening or at least one relapse within 24 months plus at least one gadolinium-enhancing lesion within 12 months before screening. Participants were randomly assigned 1:1:1 by a blocked algorithm stratified by country and baseline EDSS score to at least 12 months treatment of either once-daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment assignment. The primary endpoint was annualised relapse rate (ARR) during the treatment period and was assessed in the intention-to-treat population. Safety was assessed in all participants according to the highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, number NCT02294058 and EudraCT, number 2014–002320–27.
Between Dec 18, 2014, and Nov 12, 2015, 1346 participants were enrolled and randomly assigned to ozanimod 1·0 mg (n=447), ozanimod 0·5 mg (n=451), or interferon beta-1a (n=448). 91 (6·8%) participants discontinued the study drug (29 in the ozanimod 1·0 mg group; 26 in the ozanimod 0·5 mg group; and 36 in the interferon beta-1a group). Adjusted ARRs were 0·35 (0·28–0·44) for interferon beta-1a, 0·18 (95% CI 0·14–0·24) for ozanimod 1·0 mg (rate ratio [RR] of 0·52 [0·41–0·66] vs interferon beta-1a; p<0·0001), and 0·24 (0·19–0·31) for ozanimod 0·5 mg (RR 0·69 [0·55–0·86] vs interferon beta-1a; p=0·0013). Few ozanimod-treated participants discontinued treatment because of adverse events (13 [2·9%] who received ozanimod 1·0 mg; seven [1·5%] who received ozanimod 0·5 mg; and 16 [3·6%] who received interferon beta-1a). No first-dose, clinically significant bradycardia or second-degree or third-degree atrioventricular block was reported. The incidence of serious adverse events was low and similar across treatment groups (13 [2·9%] participants who received ozanimod 1·0 mg; 16 [3·5%] who received ozanimod 0·5 mg; and 11 [2·5%] who received interferon beta-1a). No serious opportunistic infections occurred in ozanimod-treated participants.
In participants with relapsing multiple sclerosis treated for at least 12 months, ozanimod was well tolerated and demonstrated a significantly lower relapse rate than interferon beta-1a. These findings provide support for ozanimod as an oral therapy for individuals with relapsing multiple sclerosis.
Celgene International II.</description><subject>Bradycardia</subject><subject>Brain research</subject><subject>Chicken pox</subject><subject>Clinical trials</subject><subject>Drug dosages</subject><subject>Edema</subject><subject>Gadolinium</subject><subject>Heart</subject><subject>Heart rate</subject><subject>Infections</subject><subject>Interferon</subject><subject>Ligands</subject><subject>Lymphocytes</subject><subject>Magnetic resonance imaging</subject><subject>Multiple sclerosis</subject><subject>Safety</subject><subject>Sphingosine 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Ludwig ; Selmaj, Krzysztof W ; Bar-Or, Amit ; Arnold, Douglas L ; Steinman, Lawrence ; Hartung, Hans-Peter ; Montalban, Xavier ; Kubala Havrdová, Eva ; Cree, Bruce A C ; Sheffield, James K ; Minton, Neil ; Raghupathi, Kartik ; Ding, Ning ; Cohen, Jeffrey A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-5ab3aff0cd5b6a8dafad8d44b95db996f27be0985f45b2eae000c6045bf4cee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Bradycardia</topic><topic>Brain research</topic><topic>Chicken pox</topic><topic>Clinical trials</topic><topic>Drug dosages</topic><topic>Edema</topic><topic>Gadolinium</topic><topic>Heart</topic><topic>Heart rate</topic><topic>Infections</topic><topic>Interferon</topic><topic>Ligands</topic><topic>Lymphocytes</topic><topic>Magnetic resonance imaging</topic><topic>Multiple sclerosis</topic><topic>Safety</topic><topic>Sphingosine 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Comi, Giancarlo</au><au>Kappos, Ludwig</au><au>Selmaj, Krzysztof W</au><au>Bar-Or, Amit</au><au>Arnold, Douglas L</au><au>Steinman, Lawrence</au><au>Hartung, Hans-Peter</au><au>Montalban, Xavier</au><au>Kubala Havrdová, Eva</au><au>Cree, Bruce A C</au><au>Sheffield, James K</au><au>Minton, Neil</au><au>Raghupathi, Kartik</au><au>Ding, Ning</au><au>Cohen, Jeffrey A</au><aucorp>SUNBEAM Study Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial</atitle><jtitle>Lancet neurology</jtitle><addtitle>Lancet Neurol</addtitle><date>2019-11-01</date><risdate>2019</risdate><volume>18</volume><issue>11</issue><spage>1009</spage><epage>1020</epage><pages>1009-1020</pages><issn>1474-4422</issn><eissn>1474-4465</eissn><abstract>Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 study showed that ozanimod had better efficacy than placebo on MRI measures, with a favourable safety profile, in participants with relapsing multiple sclerosis. The SUNBEAM study aimed to assess the safety and efficacy of ozanimod versus intramuscular interferon beta-1a in participants with relapsing multiple sclerosis.
SUNBEAM was a randomised, double-blind, double-dummy, active-controlled phase 3 trial done at 152 academic medical centres and clinical practices in 20 countries. We enrolled participants aged 18–55 years with relapsing multiple sclerosis, baseline expanded disability status scale (EDSS) score of 0·0–5·0, and either at least one relapse within the 12 months before screening or at least one relapse within 24 months plus at least one gadolinium-enhancing lesion within 12 months before screening. Participants were randomly assigned 1:1:1 by a blocked algorithm stratified by country and baseline EDSS score to at least 12 months treatment of either once-daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment assignment. The primary endpoint was annualised relapse rate (ARR) during the treatment period and was assessed in the intention-to-treat population. Safety was assessed in all participants according to the highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, number NCT02294058 and EudraCT, number 2014–002320–27.
Between Dec 18, 2014, and Nov 12, 2015, 1346 participants were enrolled and randomly assigned to ozanimod 1·0 mg (n=447), ozanimod 0·5 mg (n=451), or interferon beta-1a (n=448). 91 (6·8%) participants discontinued the study drug (29 in the ozanimod 1·0 mg group; 26 in the ozanimod 0·5 mg group; and 36 in the interferon beta-1a group). Adjusted ARRs were 0·35 (0·28–0·44) for interferon beta-1a, 0·18 (95% CI 0·14–0·24) for ozanimod 1·0 mg (rate ratio [RR] of 0·52 [0·41–0·66] vs interferon beta-1a; p<0·0001), and 0·24 (0·19–0·31) for ozanimod 0·5 mg (RR 0·69 [0·55–0·86] vs interferon beta-1a; p=0·0013). Few ozanimod-treated participants discontinued treatment because of adverse events (13 [2·9%] who received ozanimod 1·0 mg; seven [1·5%] who received ozanimod 0·5 mg; and 16 [3·6%] who received interferon beta-1a). No first-dose, clinically significant bradycardia or second-degree or third-degree atrioventricular block was reported. The incidence of serious adverse events was low and similar across treatment groups (13 [2·9%] participants who received ozanimod 1·0 mg; 16 [3·5%] who received ozanimod 0·5 mg; and 11 [2·5%] who received interferon beta-1a). No serious opportunistic infections occurred in ozanimod-treated participants.
In participants with relapsing multiple sclerosis treated for at least 12 months, ozanimod was well tolerated and demonstrated a significantly lower relapse rate than interferon beta-1a. These findings provide support for ozanimod as an oral therapy for individuals with relapsing multiple sclerosis.
Celgene International II.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31492651</pmid><doi>10.1016/S1474-4422(19)30239-X</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1474-4422 |
| ispartof | Lancet neurology, 2019-11, Vol.18 (11), p.1009-1020 |
| issn | 1474-4422 1474-4465 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2286945287 |
| source | Elsevier ScienceDirect Journals |
| subjects | Bradycardia Brain research Chicken pox Clinical trials Drug dosages Edema Gadolinium Heart Heart rate Infections Interferon Ligands Lymphocytes Magnetic resonance imaging Multiple sclerosis Safety Sphingosine 1-phosphate Studies |
| title | Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial |
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